Patient Preference and Adherence
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Patients’ Preference for Long-Acting Injectable
versus Oral Antipsychotics in Schizophrenia:
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Results from the Patient-Reported Medication
Preference Questionnaire
Clifton Blackwood 1
Panna Sanga 2
For personal use only.
Isaac Nuamah 3
Alexander Keenan 4
Arun Singh 2
Maju Mathews 2
Srihari Gopal 2
1
Penn State University, Abington, PA,
USA; 2Department of Neuroscience,
Janssen Research & Development, LLC,
Titusville, NJ, USA; 3Clinical Biostatistics,
Janssen Research & Development, LLC,
Titusville, NJ, USA; 4Health Economics
and Market Access, Janssen Research &
Development, LLC, Titusville, NJ, USA
Correspondence: Srihari Gopal
Email sgopal2@its.jnj.com
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http://doi.org/10.2147/PPA.S251812
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ORIGINAL RESEARCH
This article was published in the following Dove Press journal:
Patient Preference and Adherence
Introduction: Understanding patients’ preferences for long-acting injectable (LAI) or oral
antipsychotics (pills) could help reduce potential barriers to LAI use in schizophrenia.
Methods: Post hoc analyses were conducted from a double-blind, randomized, non-inferiority
study (NCT01515423) of 3-monthly vs 1-monthly paliperidone palmitate in patients with
schizophrenia. Data from the Medication Preference Questionnaire, administered on day 1
(baseline; open-label stabilization phase), were analyzed. The questionnaire includes four sets
of items: 1) reasons for general treatment preference based on goals/outcomes and preference for
LAI vs pills based on 2) personal experience, 3) injection-site (deltoid vs gluteal), 4) dosing
frequency (3-monthly vs 1-monthly). A logistic regression analysis was performed to assess the
effect of baseline variables on preference (LAIs or pills).
Results: Data from 1402 patients were available for analysis. Patients who preferred LAIs
recognized these outcomes as important: “I feel more healthy” (57%), “I can get back to my
favorite activities” (56%), “I don’t have to think about taking my medicines” (54%). Most
common reasons for medication preference (LAI vs pills) were: “LAIs/pills are easier for me”
(67% vs 18%), “more in control/don’t have to think about taking medicine” (64% vs 14%), “less
pain/sudden symptoms” (38% vs 18%) and “less embarrassed” (0% vs 46%). Majority of
patients (59%) preferred deltoid over gluteal injections (reasons: faster administration [63%],
easier [51%], less embarrassing [44%]). In total, 50% of patients preferred 3-monthly over
1-monthly (38%) or every day (3%) dosing citing reasons: fewer injections [96%], fewer
injections are less painful [84%], and fewer doctor visits [80%]. From logistic regression
analysis, 77% of patients preferred LAI over pills; culture and race appeared to play a role in
this preference.
Conclusion: Patients who preferred LAI antipsychotics prioritized self-empowerment and
quality-of-life-related goals. When given the option, patients preferred less-frequent, quar-
terly injections over monthly injections and daily oral medications.
Keywords: long-acting injectable antipsychotics, oral antipsychotics, paliperidone
palmitate, patient preference, quality-of-life
Introduction
Medication nonadherence and subsequent relapses amplify the disease burden and
contribute to worsening symptomatology and prognosis in schizophrenia.1,2
Continuous antipsychotic treatment is therefore a formidable goal in schizophrenia
management. Long-acting injectable (LAI) antipsychotics reduce adherence demands
Patient Preference and Adherence 2020:14 1093–1102 1093
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 Blackwood et al
by eliminating the need for daily dosing and maintaining
stable therapeutic drug levels for longer intervals and lower
the risk of relapse and rehospitalization due to treatment
discontinuation.2–4 Despite these benefits, LAI prescription
rates in clinical practice in most Western countries are low
and vary between 20% and 33% and are restricted to patients
who are previously nonadherent to oral antipsychotics and
Patient Preference and Adherence downloaded from https://www.dovepress.com/ by 84.54.58.107 on 08-Aug-2020
those who prefer and most likely would accept LAIs.5–8 The
disparity in percentage of patients currently being treated
with LAIs and the rate of nonadherence in patients with
schizophrenia (40% to 80%) indicates underutilization of
LAIs.9
Patients’ perceptions and attitudes are critical factors that
determine medication adherence and are also recognized as
potential barriers to LAI usage, thus underscoring the rele-
vance of patient-centric care in schizophrenia.10–12 Although
several studies have centered on clinician’s and caregiver’s
perspective, fewer studies highlight the perspective of
For personal use only.
patients with schizophrenia on choice of LAIs or oral anti-
psychotic pills. In a population-based survey of patients with
schizophrenia, patients’ acceptance of LAI antipsychotics
was found to be higher than the prescription rate.13 Further,
a dichotomy in appraising treatment goals has been observed
between patients and clinicians that could have an impact on
treatment selection and continuity.14,15 Given the wide-
ranging symptomatic and functional effects of antipsychotic
medications, understanding the patient’s treatment expecta-
tions and medication preference could help achieve concor-
dance between treatment goals, enhance patient engagement
and facilitate utilization of LAIs in schizophrenia.15
The aim of this analysis was to assess factors that deter-
mine patient’s preference for LAI or oral antipsychotics
(pills) in schizophrenia. Patient-reported outcomes to the
Medication Preference Questionnaire (MPQ) collected during
a phase 3, randomized, double-blind (DB) study of 3-monthly
paliperidone palmitate (PP3M) and 1-monthly paliperidone
palmitate (PP1M) were analyzed to assess preference to LAI
versus oral antipsychotics (pills) in schizophrenia.
Patients and Methods
Study Overview
This was a post hoc analysis of MPQ data derived from
a phase 3 (NCT01515423), randomized, multicenter, non-
inferiority study of PP3M versus PP1M.16 Detailed meth-
ods have been reported elsewhere. Briefly, the study
included adult patients with schizophrenia (Diagnostic
and Statistical Manual of Mental Disorders, 4th Edition,
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DSM-IV criteria), a Positive and Negative Syndrome
Scale total score between 70 and 120 at screening and
baseline and worsening of symptoms. After an approxi-
mately 3-week screening phase, all patients were stabilized
on PP1M in a 17-week open-label (OL) phase. Clinically
stabilized patients were then randomized to receive fixed
dose of either PP3M (175, 263, 350, or 525 mg eq.) or
PP1M (50, 75, 100, or 150 mg eq.) as deltoid or gluteal
injections in the 48-week DB treatment phase. The study
was conducted in accordance with the Declaration of
Helsinki. The protocol was approved by the relevant
Independent Ethics Committee or Institutional Review
Board (listed in Supplementary material) for each country
in which the trial was conducted and all patients provided
written informed consent.
The MPQ was administered on day 1 (first visit of the OL
phase); day 120 (first visit of the DB phase); and at the end of
study visit to assess medication preferences of patients for
PP3M relative to prior oral and/or LAI antipsychotics.
Medication Preference Questionnaire
The MPQ is a 4-page questionnaire to be completed by
patients (Figure 1). Items in page 1 gauged the importance of
general treatment goals/outcomes including symptoms, side
effects, and general well-being with regard to treatment pre-
ference. Responses were captured as “Important,” “Not
Important” and “Not sure.” In page 2, patients were asked to
indicate specific reasons (eg convenience, pain, etc.) for their
preference for LAI or oral/pills. Page 3 included questions to
understand the reasons (eg pain, comfort, etc.) for the patient’s
preference for deltoid vs gluteal injections. Items on page 4
collected information on patient’s preference based on dosing
frequency (daily, every month or every 3 months) and reasons
for preference for 1-monthly vs 3-monthly injections.
Responses for items on pages 2, 3 and 4 were captured as
“Yes,” “No” and “Not sure.”
Analysis
MPQ data collected on day 1 were used for this post hoc
analysis to minimize bias. Since the study disallowed LAI
use within 4 weeks prior to entry, we focused our MPQ
analyses on the day 1 visit. As the study utilized a double-
dummy technique, the baseline (day 1) visit is the only
timepoint when patients would not have received any study
medication. Patients were further grouped by baseline pre-
ference (either oral or LAI).
Individual items on page 1 were grouped to give a clear
understanding on the importance of specific treatment
Patient Preference and Adherence 2020:14
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Figure 1 Medication preference questionnaire.
outcomes for patients. The patient preference domains were
grouped into categories as follows: 1) patient empowerment 2)
quality-of-life and treatment adherence and 3) symptom
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Blackwood et al
improvement. The categories were created in accordance
with clinical judgment based largely on how the individual
MPQ items covered the same construct.
Responses of “Not sure” were grouped with “Not
Important” (page 1) or “No” (pages 2/3/4) under the premise
that any non-positive value is considered a negative response.
Descriptive analyses of the baseline variables were
performed with categorical variables summarized as fre-
quencies and proportions and continuous variables as
means and standard deviations. Patients’ responses to
items of MPQ were summarized descriptively.
A logistic regression analysis was conducted to assess
the effect of selected baseline variables on preference for
LAIs/pills. Continuous variables were initially categorized
(Table 1). These categorized baseline predictor variables
were first fitted individually into each model to assess their
univariate (unadjusted) effect, and then together to assess
their adjusted effect on preference for LAIs/pills.
Results
Patient Disposition
Of 1429 patients who enrolled and were dosed in the OL
phase, data were available for 1402 patients for this analysis.
Patients had a mean (SD) age of 38.4 (11.9) years and the
majority were men (55%). Patients were mostly White
(54%); 8% of patients were Black or African American and
38% belonged to other races (mostly Asian). Twelve percent
(12%) of patients were from the United States (Table 1).
Medication Preference Questionnaire
Page 1: General Treatment Preference Based on
Goals/Outcomes
Patients who preferred LAIs regarded these outcomes as
important: “I feel more healthy” (57%), “I can get back to
my favorite activities” (56%), “I don’t have to think about
taking my medicines” (54%) (Figure 2). Overall, outcomes
related to patient empowerment and quality-of-life were
regarded as important among patients who preferred LAIs.
Page 2: Preference Based on Personal Experience
Most common reasons quoted for medication preference (LAI
vs pills) were: “LAIs/pills are easier for me” (67% vs 18%),
“more in control/don’t have to think about taking medicine”
(64% vs 14%), “less pain/sudden symptoms” (38% vs 18%)
and “less embarrassed” (0% vs 46%) (Figure 3). The most
common reason cited by patients who preferred oral pills was
“I feel less embarrassed while taking pills” (46%) and “I feel
less pain while taking pills” (18%).
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Table 1 Demographics and Baseline Characteristics “fewer doctor visits” (80%) were the common reasons for
Characteristics Preference Total inclination toward the 3-monthly option. Patients who pre-
n=1402 ferred 1-monthly LAI cited “my dose can be changed” and
LAI Oral
“don’t like taking much medicine at once” as reasons.
n=1082 (Pills)
n=320

Age (years), mean (SD) 38.2 (11.8) 39.0 (12.1) 38.4 (11.9) Medication Preference and Baseline
Characteristics
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Sex, n (%)
Men 575 (53.1) 187 (58.4) 762 (54.4) A total of 1080 (77%) patients included in the logistic
Race, n (%)
regression analysis preferred LAIs over pills (Table 1).
White 640 (59.1) 120 (37.5) 760 (54.2) Preference for LAI was highest among White (84.2%)
Black 64 (5.9) 47 (14.7) 111 (7.9) followed by other racial groups (71.2%) and Black
Others 378 (34.9) 153 (47.8) 531 (37.9)
(57.7%) patients. When compared by geographic region,
Age at schizophrenia diagnosis 27.6 (9.1) 27.2 (9.3) 27.5 (9.2) preference was highest in patients from Europe (88.0%) as
(years), mean (SD) compared with patients from the United States (59.1%),
Number of prior hospitalizations, and rest of the world (70.7%). In the United States, pre-
n (%) ference for LAIs was comparable across different racial
None 340 (31.4) 105 (32.8) 445 (31.7)
groups (Blacks, 59.6%; Whites, 58.8% and others, 57.1%).
One 329 (30.4) 92 (28.8) 421 (30.0)
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≥Two 413 (38.2) 123 (38.4) 536 (38.2) In the logistic regression analysis, race (White) and coun-
try (United States) showed a significant association
Duration of prior hospitalizations
(days), n (%)
(p<0.001) with patient preference for LAIs or pills, sug-
0–14 419 (47.6) 124 (51.4) 543 (48.4) gesting the role of culture or race in preference to LAIs/
15–30 102 (11.6) 26 (10.8) 128 (11.2) pills. The unadjusted and adjusted results (odds ratio and
>30 359 (40.8) 91 (37.8) 450 (40.1)
their statistical significance) were comparable (Table 2).
BMI, n (%)
Normal 472 (43.6) 140 (43.8) 612 (43.7)
Overweight 351 (32.4) 101 (31.6) 452 (32.2) Discussion
Obese 259 (23.9) 79 (24.7) 338 (24.1) Results from this post hoc analysis of patient-reported
Country/Region, n (%)
MPQ provide insights into factors that influence
North America (USA) 97 (8.9) 67 (20.9) 164 (11.7) a patient’s inclination for treatment with either LAI or
Europe 557 (51.5) 76 (23.8) 633 (45.1) oral antipsychotics (pills) in treatment of schizophrenia.
Other 428 (39.6) 177 (55.3) 605 (43.2)
The analysis emphasized the delineation of different seg-
Abbreviations: BMI, body mass index; SD, standard deviation; USA, United States ments of treatment goals that patients regard as meaningful
of America.
and expect to achieve from their treatment. Overall, in this
study, the attitude of patients with schizophrenia regarding
Page 3: Preference Based on Injection-Site: Deltoid vs LAI antipsychotics was positive.
Gluteal Patient empowerment and quality-of-life-related goals
The majority of patients (59%) preferred deltoid over were important for patients who preferred LAI antipsycho-
gluteal injections and cited faster administration (63%), tics over oral pills. The majority of interviewed patients who
easier use (51%) and less embarrassing (44%) as reasons preferred LAIs considered general well-being, attainment of
for their choice (Figure 4). Among patients who favored clinical goals (eg reduction in symptoms), enhanced self-
gluteal injections, similar reasons were cited: faster (47%), sufficiency (eg better control over medications) and func-
easier for me (35%) and less painful (34%). tional improvements (eg ability to get back to their hobbies or
favorite activities) as priorities. These observations were
Page 4: Preference Based on Dosing Frequency: Daily similar to findings from a survey in people with recent-
vs 1-Monthly vs 3-Monthly onset schizophrenia who recognized the importance of symp-
In total, 50% of patients preferred 3-monthly over 1-monthly tom alleviation and its influence on day-to-day activities and
(38%) or every day (3%) dosing (Figure 5). “Fewer injec- social interactions.15 Conversely, psychiatrists acknowledge
tions” (96%), “fewer injections are less painful” (84%) and symptom control, relapse prevention and magnitude of side

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Figure 2 Treatment goals/outcomes cited as important or not important for medication preference.
Abbreviation: LAI, long-acting injectable.

Figure 3 Reasons for preference for LAI vs oral antipsychotics.

Abbreviation: LAI, long-acting injectable.

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Figure 4 Reasons for injection-site preference: deltoid vs gluteal.
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effects as primary factors driving LAI use and often under-
value improvements in ability to work and perform chores of
daily living and importance of independent living.14,17
Although healthcare professionals often consider fear of
needles or injection pain as a salient barrier to LAI use, only
18% of patients in this study cited less pain as the reason
for choosing oral pills over LAI antipsychotics.18,19
Embarrassment and vulnerability during administration of
injections (especially gluteal) have a coercive influence on
patients’ choice of mode of administration.20,21 As antici-
pated, embarrassment was cited as a common reason for
choosing oral antipsychotics over LAIs by patient respon-
dents in this study. Furthermore, a majority of patients pre-
ferred the less intrusive deltoid arm injections over gluteal
buttock injections and cited the reasons for their preference
as faster, easier and less embarrassing. This observation
concurs with our previous study of PP1M in patients with
schizophrenia who preferred deltoid over gluteal injections,
quoting similar reasons in their responses to the MPQ.22
There were no gender differences with regard to the prefer-
ence for site of administration and both men (60%) and
women (57%) preferred deltoid injections. Thus, availability
of LAI antipsychotics as deltoid and gluteal injections is
perceived as an important advantage by patients and psychia-
trists alike and is expected to enhance LAI acceptability.17,21
Extended dosing intervals of LAIs offer convenient dos-
ing and objective monitoring of adherence.2 Infrequent doc-
tor visits and its negative impact on the doctor-patient
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alliance, restrictions with dose titration, and possibility of
not identifying early signs of adverse events or worsening of
symptoms have been perceived as possible challenges with
LAIs.23 As PP3M is the only available LAI with a 3-monthly
dosing option, the MPQ included questions to gauge patient’s
preference for dosing frequency.24 It was observed that given
a choice, patients preferred less-frequent, quarterly injections
over monthly injections and daily oral medications. Patients
had a higher inclination to prefer PP3M over PP1M; fewer
injections, experiencing less pain due to fewer injections and
reduced doctor visits were cited as reasons driving their
choice. Patients preferring PP1M considered the flexibility
to change dose as an advantage over the longer dosing inter-
val of PP3M.
Notably, this is the largest study to date where patient
preference for LAIs was collected in a systematic and con-
trolled fashion. Observations from the current analysis sup-
port the recent guideline issued by the American Psychiatric
Association, which briefly mentions LAI use in the context of
patient preference for LAIs, frequency of dosing and site of
injection.25 It recommends the use of LAI antipsychotics in
patients who prefer LAIs or who have a history of compro-
mised adherence.25 We suggest that international guidelines
should place greater emphasis on patient preference, as this
ultimately will lead to greater adherence, treatment satisfac-
tion and better treatment outcomes.
In the logistic regression analysis, among the socio-
demographic factors, only race and geographic region
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Figure 5 Medication preference based on dosing frequency and reasons for preference.
Abbreviation: LAI, long-acting injectable.
appeared to have a significant influence suggesting the role
of race and culture in patient preference. Preference for LAI
was highest among Whites followed by other racial groups.
When compared by geographic region, preference for LAIs
was highest in Europe compared to the United States or the
rest of the world. In this study, preference for LAIs was
comparable between the racial groups in the United States.
However, in a chart-based retrospective analysis in the
United States, Whites were less likely to receive LAI anti-
psychotics as compared to non-Whites and Blacks.26
The current results may have potential limitations inher-
ent to a post hoc analysis. As the analysis involved patients
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Blackwood et al
enrolled in a randomized study, the assessment of pragmatic
viewpoint may be missing as the patients were willing to
participate in the study, thereby excluding patients with poor
treatment adherence.23 Additionally, the study population
does not accurately represent the real-word scenario as
patients at risk of suicide and those with recent substance
dependence, or clinically relevant medical diagnoses were
excluded.16 To provide a comprehensive perspective on
patient preference, additional studies are needed that include
patient populations closely representing clinical practice and
real-world settings. In addition, these studies should also
examine the adverse event profile and efficacy of LAI
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Table 2 Effect of Baseline Characteristics on Patients’ Medication Preference (LAI vs Pills)

Variable Unadjusted Adjusted

Odds Ratio (95% CI) p-value Odds Ratio (95% CI) p-value

Race (White) 2.41 (1.87; 3.12) <0.001 2.39 (1.77; 3.23) <0.001
Country (USA) 0.87 (0.81; 0.92) <0.001 0.41 (0.27; 0.62) <0.001
Sex (Women) 1.24 (0.96; 1.60) 0.095 1.25 (0.92; 1.70) 0.150
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Age (18–50 years) 1.05 (0.80; 1.38) 0.696 1.08 (0.73; 1.59) 0.710
BMI (normal) 0.99 (0.77; 1.28) 0.968 0.95 (0.70; 1.30) 0.745
Age of diagnosis (≤25 years) 0.81 (0.63; 1.03) 0.088 0.88 (0.65; 1.19) 0.410
Number of prior psychiatric hospitalizations (none) 0.94 (0.72; 1.22) 0.639 1.38 (0.91; 2.09) 0.127
Duration of prior hospitalizations (≤30 days) 0.88 (0.65; 1.18) 0.394 1.09 (0.71; 1.66) 0.699
Abbreviations: BMI, body mass index; CI, confidence interval; USA, United States of America.

antipsychotics versus oral antipsychotics considering the
pharmacokinetic differences associated with route to admin-
istration and its potential impact on tolerability and
adherence.27,28 Furthermore, it has been observed that patient
For personal use only.
and discuss the possible risks and benefits. By addressing
patients’ concerns and treatment objectives, clinicians can
encourage adherence and increase the likelihood of achiev-
ing the targeted goals.

acceptance of LAIs improves with experience.13 Thus, as

MPQ responses collected only on day 1 (before administra-
tion of PP3M and PP1M) were analyzed, patient acceptance
of LAI antipsychotics would be expected to improve over
time.
Conclusions
Patients who entered this study in general preferred LAIs
over oral antipsychotics as a treatment choice. Patients who
preferred LAI antipsychotics focused on achieving patient
empowerment and quality-of-life-related goals. Additionally,
patients showed a higher preference for PP3M (3-monthly
LAI) than PP1M (1-monthly LAI), citing convenience and
better control as reasons for their choice. Better understand-
ing of patients’ treatment priorities and perspective could
help overcome barriers to LAI use and inform the best course
of personalized schizophrenia treatment for improved patient
satisfaction and medication adherence. LAIs have been his-
torically underutilized to address adherence in schizophrenia,
mainly because of the perception that patients are less accept-
ing. Our study shows that when given an option, patients are
very willing to consider LAI antipsychotics. Thus, clinicians
should initiate open communication with patients as well as
their caregivers at the start of treatment to become more
attuned to patients’ treatment preferences and foster patient-
centric management. Face-to-face discussion using simple
in-clinic semi-structured interviews could help gauge
patients’ preferences, fears and quandaries related to route
of treatment administration and educate patients about LAIs
Prior Publications
Data from this post hoc analysis were presented as a poster at
the Psych Congress 2019, October 03–06, San Diego,
California and e-posters were presented at the Society
of Biological Psychiatry (SOBP) and Schizophrenia
International Research Society (SIRS) 2020 Virtual Annual
Meetings.
Acknowledgments
This study was sponsored by Janssen Research &
Development, LLC. Priya Ganpathy, MPharm CMPP
(SIRO Clinpharm Pvt. Ltd., India) provided writing assis-
tance and Ellen Baum, PhD (Janssen Global Services,
LLC) provided additional editorial support. The authors
also thank the patients and investigators for their partici-
pation in the study.
Author Contributions
All authors made substantial contributions to conception
and design, acquisition of data, or analysis and interpreta-
tion of data; took part in drafting the article or revising it
critically for important intellectual content; gave final
approval of the version to be published; and agree to be
accountable for all aspects of the work.
Disclosure
PS, IN, AK, AS, MM and SG are employees of Janssen
Research & Development, LLC and hold company stocks.

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CB is a student at Pennsylvania State University and was
working as a summer intern at Janssen Research &
Development, LLC. The authors report no other conflicts
of interest in this work.
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